Mass spectrometers are widely used in analytical chemistry. Analysis of a sample used in a mass spectrometer requires the production of analyte ions. Ion sources are well known in the art and may be divided into two groups: vacuum ionization ion sources and atmospheric pressure ionization sources. The second group, atmospheric pressure ionization sources, includes atmospheric pressure chemical ionization and Electrospray Ionization (ESI). To sample atmospheric pressure ions a mass spectrometer must be equipped with Atmospheric Pressure Interface (API) to transfer ions from an external region of atmospheric pressure to a mass analyzer under high vacuum.
Two significant recent advancements have expedited the development of mass spectrometry as a tool in analytical chemistry. These are Matrix Assisted Laser Desorption Ionization (MALDI) and Electrospray Ionization (ESI) techniques. Both MALDI and ESI enable the production of intact heavy molecular ions from a condensed phase (solid phase for MALDI and liquid phase for ESI). The advantages of MALDI include simplicity of sample preparation, stability, and high tolerance to sample contamination. An API is used to transfer ions from an atmospheric pressure ion source, to the vacuum of a mass spectrometer. This interface has a low efficiency and, consequently, atmospheric pressure MALDI has not been widely applied because of the concern that not enough ions are generated to compensate for the loss of ions due to the API.
Franzen et al. developed a method, disclosed in U.S. Pat. No. 5,663,562, for ionizing heavy analyte molecules deposited on a solid support in a gas at atmospheric pressure. The analyte molecules' are deposited together with decomposable (explosive) matrix material and then blasted into the surrounding gas under atmospheric pressure as a result of decomposition of matrix material under laser irradiation. Neutral gas-phase analyte molecules are produced at this stage which are then ionized by atmospheric pressure chemical ionization for further analysis by a mass spectrometer.
An Atmospheric Pressure Matrix Assisted Laser Desorption (AP-MALDI) apparatus is described in U.S. Pat. No. 5,965,884. The '884 patent describes a system wherein MALDI-type spectra can be recorded using any type of mass spectrometer equipped with API without essential modifications. The AP-MALDI apparatus described in the '884 patent has three parts: an atmospheric pressure ionization chamber which hosts a sample to be analyzed; a laser system outside the ionization chamber for illuminating the sample in the ionization chamber; and an interface which connects the ionization chamber to the spectrometer. The ionization chamber is filled with a non-reactive bath gas at or near atmospheric pressure. The ionization chamber has a window through which the illuminating laser beam enters. The sample typically is a mixture of analyte materials and light-absorbing matrix substances. The sample is deposited on the surface of a support. When illuminated with the laser beam, the matrix molecules are ionized and evaporated. The ionized matrix molecules ionize the analyte molecules through a charge transfer process. The interface between the ionization chamber and the spectrometer has an inlet orifice to allow the ionized analyte to enter the spectrometer. The laser system comprises a pulsed laser and optics. The laser beam is focused by a focusing lens positioned outside the ionization chamber.
AP-MALDI takes place under atmospheric pressure conditions. The AP-MALDI technique provides a stable ion supply to the mass spectrometer.
Since the initial reports of atmospheric pressure-matrix-assisted laser desorption/ionization (AP-MALDI; Laiko U V, Moyer S C, Cotter R J., 2000, Analytical Chemistry 72:5239-5243; Keough T, Lacey M P, Strife R J. Rapid Communications in Mass Spectrometrey), several laboratories have been pursuing the development of AP-MALDI, (Moyer S C, Cotter R J, Woods A S, 2002, Journal of the American Society for Mass Spectrometry 13:274-283; Galicia M C, Vertes A, Callahan J H, 2002, Analytical Chemistry 74:1891-1895; Creaser C S, Reynolds J C, Harvey D J, 2002, Rapid Communications in Mass Spectrometry 16:176-184; Moyer S C, Cotter R J., 2002, Analytical Chemistry 74:469A-476A; Laiko V V, Taranenko N I, Berkout V D, Yakshin M A, Prasad C R, Lee S H, Doroshenko, V M, 2002, Journal of the American Society for Mass Spectrometry 13:354-361; Laiko V V, Taranenko N I, Berkout V D, Musselman, Doroshenko V M, 2002, Rapid Communications in Mass Spectrometry 16:1737-1742) atmospheric pressure laser desorption/ionization from porous silicon (AP-DIOS), and laser desorption-atmospheric pressure chemical ionization (LD-APCI) (Coon, J J, McHale, K J, Harrison, W W, 2002, Rapid Communications in Mass Spectrometry 16:681-685; Coon J J, Harison W W, 2002, Analitical Chemistry 74).
Though each of these AP-Laser Desorption techniques may possess certain advantages with respect to the others, they also share some important similarities. First, quadrupole ion trap mass spectrometers (QIT-MS) have been used almost exclusively for AP-laser desorption studies; second, each of the methods employs an absorbing analyte-containing matrix to effect either the desorption/ionization of gas-phase analyte ions (AP-MALDI, AP-DIOS) or the desorption of gas-phase analyte molecules (LD-APCI). Therefore, studies aimed to understand the basic processes in AP-laser desorption (AP-LD) could play a significant role in their continued development.
Interest in AP-MALDI has stimulated QIT-MS manufacturers to develop and make available commercial interfaces. Despite this interest, surprisingly little effort has been reported on the fundamental processes common to all AP-LD procedures. Though AP-LD methods are seemingly straightforward, knowledge of such processes will almost certainly be a prerequisite for their optimal employment in mass spectrometry.
Unlike vacuum MALDI-TOF-MS instruments, AP-LD-QIT-MS allows the accumulation of ions generated from multiple laser pulses into a single mass analysis event. Indeed, the majority of the reported AP-LD experiments have taken advantage of this opportunity by asynchronously coupling laser pulses (˜10 Hz) with fixed ion trapping periods of (˜200-500 ms) (Keough T, Lacey M P, Strife R J. Rapid Communications in Mass Spectrometrey; Moyer S C, Cotter R J, Woods A S, 2002, Journal of the American Society for Mass Spectrometry 13:274-283; Galicia M C, Vertes A, Callahan J H, 2002, Analytical Chemistry 74:1891-1895; Creaser C S, Reynolds J C, Harvey D J, 2002, Rapid Communications in Mass Spectrometry 16:176-184; Moyer S C, Cotter R J, 2002, Analytical Chemistry 74:469A-476A; Laiko V V, Taranenko N I, Berkout V D, Yakshin M A, Prasad C R, Lee S H, Doroshenko, V M, 2002, Journal of the American Society for Mass Spectrometry 13:354-361; Laiko V V, Taranenko N I, Berkout V D, Musselman, Doroshenko V M, 2002, Rapid Communications in Mass Spectrometry 16:1737-1742) In an AP-MALDI experiment, Laiko et al. report that this approach generates a quasi-continuous ion beam; (Creaser C S, Reynolds J C, Harvey D J, 2002, Rapid Communications in Mass Spectrometry 16:176-184; Moyer S C, Cotter R J, 2002, Analytical Chemistry 74:469A-476A), however, it seems unlikely that MALDI-generated ions would be continuously produced during the entire 100 ms intermission of the nanosecond laser pulses. Moreover, the temporal width of each ion pulse relative to the injection period may have important implications regarding efficient ion injection across the entire mass range. This is because most QIT-MS systems are designed to use several levels of radiofrequency (RF) amplitude during a fixed ion injection period to optimally inject ions across the entire mass range. Consequently, a fundamental understanding of the ion pulse temporal profile following AP-LD will be essential for its for optimal coupling to QIT-MS.